Possible Interaction: Glutathione and Melphalan

“Increased cellular glutathione GSH ) can mediate melphalan resistance.”

“Increased glutathione GSH ) in MM may mediate resistance to L-PAM.”

“A strong correlation was seen between in vitro melphalan dose and resultant GSH level and GST activity.”

“In vivo recurrent tumor GSH levels correlated with increasing melphalan infusion dose.”

“A direct correlation (P < 0.01) between intracellular GSH levels and the LD99 dose of melphalan was observed, signifying that elevation of the thiol secondary to GCS expression is sufficient to confer the resistance phenotype.”

“Both hyperthermia and glutathione depletion have been shown to increase the antineoplastic activity of melphalan.”

“Measurement of glutathione levels in TE-671 MR xenografts following treatment with melphalan , hyperthermia, or melphalan plus hyperthermia revealed significant reductions in glutathione content with the nadir (60% of control values) seen 6 h following treatment.”

“…,glutathione plays a role in the detoxification and repair … cellular injury by such diverse agents as mechlorethamine, melphalan , cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, … mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone).”

“However, although GSH depletion potentiated the toxicity of cisplatin and melphalan , occasionally switching the mode of death from apoptosis to necrosis, it did not affect the toxicity of the other antitumor drugs.”

“It is believed that GSH plays a role in the aquisition of resistance to anti-cancer drugs, such as a cisplatin, adriamycin, melphalan , or taxol.”

“The main conclusion from the studies of these fibroblasts is that GSH plays a significant role in the cellular resistance to cytostatic drugs such as platinum compounds and melphalan.”